Deciphering the unique autoregulatory mechanisms and substrate specificity of the understudied DCLK3 kinase linked to neurodegenerative diseases.

Protein kinases represent one of the largest and most druggable protein families. Despite considerable progress in their understanding, approximately one-third of human kinases remain poorly characterized, known as the "dark" kinome. Doublecortin-like kinase 3 (DCLK3), a member of this elusive group, has emerged for its involvement in neuroprotection in Huntington's disease and other neurodegenerative disorders.

An atlas of bacterial serine-threonine kinases reveals functional diversity and key distinctions from eukaryotic kinases.

Bacterial serine-threonine kinases (STKs) regulate diverse cellular processes associated with cell growth, virulence, and pathogenicity and are evolutionarily related to the druggable eukaryotic STKs. A deeper understanding of how bacterial STKs differ from their eukaryotic counterparts and how they have evolved to regulate diverse bacterial signaling functions is crucial for advancing the discovery and development of new antibiotic therapies. Here, we classified more than 300,000 bacterial STK sequences from the NCBI RefSeq nonredundant and UniProt protein databases into 35 canonical and seven pseudokinase families on the basis of the patterns of evolutionary constraints in the conserved catalytic domain and flanking regulatory domains.

Atlas of the Bacterial Serine-Threonine Kinases expands the functional diversity of the kinome.

Bacterial serine-threonine protein kinases (STKs) regulate diverse cellular processes associated with cell growth, virulence, and pathogenicity. They are evolutionarily related to the druggable eukaryotic STKs. However, an incomplete knowledge of how bacterial STKs differ from their eukaryotic counterparts and how they have diverged to regulate diverse bacterial signaling functions presents a bottleneck in targeting them for drug discovery efforts.